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1.
Chem Mater ; 36(7): 3128-3137, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617806

RESUMO

Lacunar spinels, represented by AM4X8 compounds (A = Ga or Ge; M = V, Mo, Nb, or Ta; X = S or Se), form a unique group of ternary chalcogenide compounds. Among them, GeV4S8 has garnered significant attention due to its distinctive electrical and magnetic properties. While previous research efforts have primarily focused on studying how this material behaves under cooling conditions, pressure is another factor that determines the state and characteristics of solid matter. In this study, we employed a diamond anvil cell in conjunction with high-energy synchrotron X-ray diffraction, Raman spectroscopy, four-point probes, and theoretical computation to thoroughly investigate this material. We found that the structural transformation from cubic to orthorhombic was initiated at 34 GPa and completed at 54 GPa. Through data fitting of volume vs pressure, we determined the bulk moduli to be 105 ± 4 GPa for the cubic phase and 111 ± 12 GPa for the orthorhombic phase. Concurrently, electrical resistance measurements indicated a semiconductor-to-nonmetallic conductor transition at ∼15 GPa. Moreover, we experimentally assessed the band gaps at different pressures to validate the occurrence of the electrical phase transition. We infer that the electrical phase transition correlates with the valence electrons in the V4 cluster rather than the crystal structure transformation. Furthermore, the computational results, electronic density of states, and band structure verified the experimental observation and facilitated the understanding of the mechanism governing the electrical phase transition in GeV4S8.

3.
BMC Musculoskelet Disord ; 22(1): 686, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384393

RESUMO

BACKGROUND: Total two-stage exchange is commonly used in clinical practice as a treatment for infected total hip arthroplasty (THA); however, this approach involves considerable limitations, including significant bone loss and severe trauma. This retrospective cohort study was conducted to evaluate clinical outcomes following the use of partial two-stage exchange (PTE) for infected THA. METHODS: We performed a retrospective analysis of 28 patients with infected THA who were treated by PTE between September 2000 and June 2019. Eligibility for PTE was limited to patients with a well-fixed femoral stem prosthesis. In the first stage of the operation, the femoral stem prosthesis was preserved; subsequently, the acetabular prosthesis, liner, and head were replaced with an antibiotic-loaded spacer. The new prosthesis was then implanted into patients and monitored for at least 3 months to ensure freedom from infection. RESULTS: Patients were followed for an average of 4 years (range, 2-11 years), with an overall success rate of 85.7% (24/28). The mean Harris hip score at the final follow-up was 76.2 ± 11.7 points. CONCLUSIONS: The findings of this study suggest that PTE could be an acceptable option for a subset of patients with infected THA, offering a satisfactory infection control rate and clinical outcomes comparable to those of total two-stage exchange, but with less harm.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Infecções Relacionadas à Prótese , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
4.
Aging (Albany NY) ; 13(1): 769-781, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33257597

RESUMO

Head and neck squamous cell carcinoma (HNSCC), which occurs frequently worldwide, is characterized by high risk of metastasis. MicroRNAs (miRNAs) play crucial roles in tumorigenesis and cancer development. In this study, miR-29c-5p was identified using three high throughput microarrays. We measure miR-29c-5p expression in HNSCC tissues and cell lines. To determine the function of miR-29c-5p in HNSCC, we evaluated its effects in vitro on cell proliferation, the cell cycle, apoptosis, and cell migration. We employed a mouse tumor xenograft model to determine the effects of miR-29c-5p on tumors generated by HNSCC cell lines. The miR-29c-5p expression was lower in HNSCC tissues than in normal tissues. Upregulated miR-29c-5p expression in HNSCC cells inhibited migration and arrested cells in the G2/M phase of the cell cycle. Further, upregulated miR-29c-5p expression inhibited the proliferation of HNSCC cells in vivo and in vitro. In addition, transmembrane protein 98 (TMEM98) was identified as a direct target of miR-29c-5p by using a luciferase reporter assay. These findings provide new insights that link the regulation of miR-29c-5p expression to the malignant phenotype of HNSCC and suggest that employing miR-29c-5p may serve as a therapeutic strategy for managing patients with HNSCC.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Proteínas de Membrana/genética , MicroRNAs/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Técnicas In Vitro , Camundongos , Transplante de Neoplasias
5.
Front Cell Dev Biol ; 8: 676, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850805

RESUMO

Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.

6.
Oncol Rep ; 44(2): 685-697, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32468011

RESUMO

Laryngeal carcinoma (LCC) is a common malignant tumor with low radiosensitivity and generally poor response rates. The ubiquitin protein ligase E3 component n­recognin 5 (UBR5) has prognostic implications in several neoplasms; however, its role in LCC and radiotherapy sensitivity remains unknown. Immunohistochemistry and bioinformatics analyses were performed to measure UBR5 protein and mRNA expression in LCC and adjacent non­tumor tissues. The gene and protein expression of UBR5 in LCC and HuLa­PC cell lines were measured using quantitative PCR and western blot analyses. Following transfection with small interfering RNA or UBR5 overexpression plasmid in LCC cells, the proliferation, cell cycle distribution, invasion, migration and radiosensitivity of LCC cells were analyzed. UBR5­related lncRNA, targeted miRNA and protein­protein interaction networks were analyzed using bioinformatics. Finally, the expression of the p38/mitogen­activated protein kinase (MAPK) pathway was evaluated following UBR5 silencing in M2E cells treated with radiation. Increased UBR5 expression was observed in LCC tissues compared with adjacent non­tumor tissues, and it was correlated with poor overall survival of LCC patients. After overexpression or silencing of UBR5 in M2E and M4E LCC cells, cell proliferation and radiosensitivity were significantly increased or decreased, respectively, compared with the control groups. The percentage of S phase cells decreased in the UBR5 si­RNA group compared with that in the control group, while overexpression of UBR5 exerted no effect on the cell cycle. In addition, the expression of Bcl­2 and p38 was decreased in the si­UBR5 combined with radiation groups. The level of phosphorylated p38 expression was increased after combination of si­UBR5 with radiation. The small molecule inhibitor of p38/MAPK signaling, SB203580, decreased the viability of UBR5­overexpressing cells and the survival fraction when cells were exposed to radiation. These findings demonstrated that UBR5 may be involved in regulating cell proliferation and sensitivity to radiotherapy in LCC via the p38/MAPK pathway, thereby highlighting its possible value for the development of new therapeutic strategies and targets for the treatment of this disease.


Assuntos
Carcinoma/patologia , Neoplasias Laríngeas/patologia , Tolerância a Radiação , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/radioterapia , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/radioterapia , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Masculino , Estadiamento de Neoplasias , Fosforilação/efeitos da radiação , Prognóstico , Regulação para Cima
7.
Am J Transl Res ; 12(1): 191-202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32051748

RESUMO

Genital warts, which are one of the most common sexually transmitted diseases (STDs), result from persistent infection with human papillomavirus (HPV), especially subtypes 6 or 11. Topical application of 5% imiquimod cream is currently recommended as a first-line treatment choice for genital warts, but the clearance and patient compliance rates remain less than sufficient. In the current study, we developed a temperature-sensitive gel that contains the host-defense peptides caerin 1.1 and 1.9, which were originally isolated from Australian tree frogs of the genus Litoria. Growth of HPV16 E6/E7-transformed TC-1 cells was inhibited in vitro and in vivo following injection of the tumor with the caerin gel in a TC-1 tumor mouse model. Furthermore, when the caerin gel was topically applied, the inhibitory effect remained, and T, NK cells were attracted to the tumor site. In addition, the gel maintained a similar level of bioactivity after incubation at room temperature for 30 days. Our results suggest that this caerin gel, following further optimization, may provide an alternative method for the management of genital warts.

8.
PLoS One ; 14(9): e0221045, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31545798

RESUMO

Human papillomavirus (HPV) related tumours account for a significant proportion of head and neck squamous cell carcinomas (HNSCCs) in developed countries. They respond better to chemo- and radio-therapy, and have a better stage specific prognosis. To establish their prevalence in China, we assessed a series of histology confirmed HNSCCs collected in Zhejiang and Guangdong provinces by PCR for HPV DNA and by immunohistochemistry for p16 protein status. Among 303 HNSCCs, HPV DNA was detected in 26.4%, with HPV16 DNA in 71% of these. Of HNSCC located in the oropharynx, 38.55% (32/83) were HPV+ve. In this series, p16 status was a relatively poor predictor of HPV status as detected by PCR. The stage specific survival time of HPV+ HNSCCs was significantly longer than for HPV- HNSCC. HPV status should be assessed for oropharyngeal cancers in China to assist with appropriate management, and prophylaxis against HPV infection should be considered to reduce the incidence of this disease.


Assuntos
Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Idoso , China/epidemiologia , Suscetibilidade a Doenças , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Medição de Risco , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida
9.
Am J Otolaryngol ; 40(6): 102280, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31519431

RESUMO

BACKGROUND: Previous studies have demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, because of the private location of inguinal lymph nodes, inguinal ILIT is relatively inconvenient. We proposed a novel form of ILIT that involves 3 injections of allergen into cervical lymph nodes. The aim of this study is to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced allergic rhinitis (AR) in adults. METHODS: In this study, we performed a prospective cohort study to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced AR in adults, by comparing the symptom scores, quality-of-life scores (QOLS) and drug scores (use of rescue medication) before and after treatment. Meanwhile, side events were also recorded. RESULTS: Cervical ILIT elicited no moderate-severe adverse events. Patients receiving cervical ILIT experienced a significant improvement in nasal symptoms, eye symptoms and quality of life, as compared to baseline (P all <0.001). A reduction in the use of rescue medication was also demonstrated (P < 0.001). CONCLUSIONS: In this first-in-human clinical study, cervical ILIT was demonstrated safe and induced allergen tolerance after 3 injections.


Assuntos
Alérgenos/administração & dosagem , Imunoterapia/métodos , Pyroglyphidae , Rinite Alérgica Perene/terapia , Adolescente , Adulto , Animais , Feminino , Humanos , Injeções Intralinfáticas , Masculino , Pessoa de Meia-Idade , Pescoço , Projetos Piloto , Qualidade de Vida , Adulto Jovem
10.
BMC Complement Altern Med ; 19(1): 163, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31277636

RESUMO

BACKGROUND: Therapeutic vaccines against cervical cancer remain ineffective. Previously, we demonstrated that blocking the signalling of a cytokine, interleukin 10, at the time of immunisation elicited significantly higher numbers of antigen specific T cells and inhibited tumour growth in mice. RESULTS: In the current paper, we demonstrate, in a HPV16 E6/E7 transformed TC-1 tumour mouse model, that despite increased antigen specific T cell numbers, blocking IL-10 signalling at the time of immunisation does not increase the survival time of the TC-1 tumour bearing mice compared to mice receiving the same immunisation with no IL-10 signalling blockade. Moreover, the function of tumour infiltrating T cells isolated 3 weeks post TC-1 transplantation is more suppressed than those isolated 2 weeks after tumour inoculation. We demonstrate that synthesized caerin peptides, derived from amphibian skin secretions, 1) were able to inhibit TC-1 tumour growth both in vitro and in vivo; 2) are environmentally stable; and 3) promote the secretion of pro-inflammatory interlukine-6 by TC-1 cells. Notably caerin peptides were able to increase the survival time of TC-1 tumour bearing mice after therapeutic vaccination with a HPV16E7 peptide-based vaccine containing IL-10 inhibitor, via recruiting increased levels of T cells to the tumour site. CONCLUSION: Caerin peptides increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site.


Assuntos
Proteínas de Anfíbios/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Vacinas Anticâncer/uso terapêutico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Proteínas de Anfíbios/uso terapêutico , Animais , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Vacinas Anticâncer/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Interleucina-10/antagonistas & inibidores , Interleucina-6/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Linfócitos T/metabolismo
11.
Cancer Immunol Immunother ; 67(11): 1719-1730, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30155576

RESUMO

The T-cell immune responses in nasopharyngeal carcinoma patients have been extensively investigated recently for designing adoptive immunotherapy or immune checkpoint blockade therapy. However, the distribution characteristics of T cells associated with NPC pathogenesis are largely unknown. We performed deep sequencing for TCR repertoire profiling on matched tumor/adjacent normal tissue from 15 NPC patients and peripheral blood from 39 NPC patients, 39 patients with other nasopharyngeal diseases, and 33 healthy controls. We found that a lower diversity of TCR repertoire in tumors than paired tissues or a low similarity between the paired tissues was associated with a poor prognosis in NPC. A more diverse TCR repertoire was identified in the peripheral blood of NPC patients relative to the controls; this was related to a significant decrease in the proportion of high-frequency TCR clones in NPC. Higher diversity in peripheral blood of NPC patients was associated with a worse prognosis. Due to the peculiarity of the Vß gene usage patterns in the peripheral blood of NPC patients, 15 Vß genes were selected to distinguish NPC patients from controls by the least absolute shrinkage and selection operator analysis. We identified 11 clonotypes shared by tumors and peripheral blood samples from different NPC patients, defined as "NPC-associated" that might have value in adoptive immunotherapy. In conclusion, we here report the systematic and overall characteristics of the TCR repertoire in tumors, adjacent normal tissues, and peripheral blood of NPC patients. The data obtained may be relevant to future clinical studies in the setting of immunotherapy for NPC patients.


Assuntos
Carcinoma/imunologia , Carcinoma/mortalidade , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/mortalidade , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Carcinoma/terapia , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/terapia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
12.
Biomed Res Int ; 2018: 7382351, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29862288

RESUMO

Caerin is a family of peptides isolated from the glandular secretion of Australian tree frogs, the genus Litoria, and has been previously shown to have anticancer activity against several cancer cells. In this work, we used two host-defence peptides, caerin 1.1 and caerin 1.9, to investigate their ability to inhibit a murine derived TC-1 cell transformed with human papillomavirus 16 E6 and E7 growth in vitro. Caerin 1.9 inhibits TC-1 cell proliferation, although inhibition is more pronounced when applied in conjunction with caerin 1.1. To gain further insights into the antiproliferative mechanisms of caerin 1.9 and its additive effect with caerin 1.1, we used a proteomics strategy to quantitatively examine (i) the changes in the protein profiles of TC-1 cells and (ii) the excretory-secretory products of TC-1 cells following caerin peptides treatment. Caerin 1.9 treatment significantly altered the abundance of several immune-related proteins and related pathways, such as the Tec kinase and ILK signalling pathways, as well as the levels of proinflammatory cytokines and chemokines. In conclusion, caerin peptides inhibit TC-1 cell proliferation, associated with modification in signalling pathways that would change the tumour microenvironment which is normally immune suppressive.


Assuntos
Proteínas de Anfíbios/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias/metabolismo , Proteômica , Transdução de Sinais/efeitos dos fármacos , Animais , Células HeLa , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia
13.
Otolaryngol Head Neck Surg ; 156(4): 622-626, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28141179

RESUMO

Objective The aim of this study was to compare the outcomes of lateral temporal bone resection and pedicled temporalis muscle flap stuffing with external auditory canal closure with those of canal wall down mastoidectomy for the treatment of mastoid osteoradionecrosis. Study Design Prospective nonrandomized case-control clinical study. Setting Department of Otolaryngology of the First People's Hospital of Foshan. Subjects and Methods Seventy-seven postirradiation nasopharyngeal carcinoma patients with mastoid osteoradionecrosis were included. Forty patients (40 ears) underwent lateral temporal bone resection in the temporalis muscle flap group. Their pedicled temporalis muscle flaps were laid on the surgical cavity, and the external canal opening was simultaneously closed. Thirty-seven patients (37 ears) underwent a canal wall down mastoidectomy in the mastoidectomy group. The surgical wounds and complications following surgery were retrospectively analyzed. Results The patients were followed for 2 years. The percentage of patients with purulent otorrhea and persistent osteoradionecrosis in the temporalis muscle flap group was lower than that in the mastoidectomy group. Conclusion Our preliminary results suggest that lateral temporal bone resection with the pedicled temporalis muscle flap filled into the surgical cavity, followed by closure of the external auditory canal, represents a valuable approach for treating mastoid osteoradionecrosis.


Assuntos
Processo Mastoide/cirurgia , Osteorradionecrose/cirurgia , Retalhos Cirúrgicos , Osso Temporal/cirurgia , Adulto , Estudos de Casos e Controles , Meato Acústico Externo/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Estudos Prospectivos , Radioterapia/efeitos adversos
14.
PLoS One ; 12(2): e0172264, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28207826

RESUMO

BACKGROUND: Potential clinical application values of certain cytokines and chemokines that participate in the process of tumor growth, invasion, and metastasis have been reported. However, there still lack of biomarkers for a great many of malignancy. This study identified cytokines or chemokines involved in the occurrence and development of nasopharyngeal carcinoma (NPC), which might be a biomarker for noninvasive early diagnosis. METHODS: The plasma levels of 19 cytokines and chemokines were detected by the luminex liquid array-based multiplexed immunoassays in 39 NPC patients before and after treatment by definitive intensity-modulated radiotherapy (IMRT). RESULTS: Plasma levels of almost all of the 19 cytokines and chemokines in NPC patients were higher than healthy controls, while only IFN-γ, IL-1b IL-6, MCP-1, TNF-α, FKN, IL-12P70, IL-2, IL-5 and IP-10 showed significant differences. However, expression levels of most of the 19 cytokines and chemokines decreased after therapy, especially IFN-γ, IL-10, IL-1b, IL-6, IL-8, MCP-1, TNF-α, VEGF, IL-17A, IL-2, IL-5 and MIP-1b, have a dramatic decline. Taking together, plasma levels of IFN-γ, IL-1b, IL-6, MCP-1, TNF-α, IL-2 and IL-5 are significantly increased in NPC patients and dramatically decreased after treatment, suggesting these cytokines and chemokines might play important roles in the progress of NPC. More interestingly, the expression level of MPC-1 is significantly associated with clinical stage. CONCLUSION: MCP-1 might involve in the genesis and development process of NPC, which might serve as a noninvasive biomarker for early diagnosis.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/sangue , Quimiocinas/sangue , Citocinas/sangue , Neoplasias Nasofaríngeas/sangue , Radioterapia de Intensidade Modulada/métodos , Adulto , Carcinoma/radioterapia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
15.
Hum Vaccin Immunother ; 13(3): 518-527, 2017 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-27686406

RESUMO

Interleukin 10 (IL-10) is a cytokine that is able to downregulate inflammation. Its overexpression is directly associated with the difficulty in the clearance of chronic viral infections, such as chronic hepatitis B, hepatitis C and HIV infection, and infection-related cancer. IL-10 signaling blockade has been proposed as a promising way of clearing chronic viral infection and preventing tumor growth in animal models. Recently, we have reported that peptides with a helical repeating pattern of hydrophobic and hydrophilic residues are able to inhibit IL-10 significantly both in vitro and in vivo. 1 In this work, we seek to further study the inhibiting mechanism of these peptides using sequence-modified peptides. As evidenced by both experimental and molecular dynamics simulation in concert the N-terminal hydrophobic peptide constructed with repeating hydrophobic and hydrophilic pattern of residues is more likely to inhibit IL10. In addition, the sequence length and the ability of protonation are also important for inhibition activity.


Assuntos
Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Interleucina-10/antagonistas & inibidores , Peptídeos/química , Peptídeos/farmacologia , Linhagem Celular , Dicroísmo Circular , Humanos , Simulação de Dinâmica Molecular , Ressonância de Plasmônio de Superfície
16.
Discov Med ; 21(116): 239-50, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27232510

RESUMO

Rapidly growing evidence has shown that long noncoding RNAs (lncRNAs) are playing more and more important roles in a variety of biological processes and have been involved in various types of cancer. How to better decode these noncoding transcripts and how to predict their potential roles in tumorigenesis particularly in nasopharyngeal carcinoma (NPC) are still open questions. In this study, we applied our custom-designed lncRNA+mRNA gene expression microarray, which contains probes against 38,141 lncRNA transcripts, to assaying the expression profiling of flash-frozen tumorous and non-tumorous tissue samples from nonkeratinizing carcinoma (NKC), which is the major histologic type of NPC. As a result, 481 differentially expressed (DE) lncRNAs (231 up-regulated and 250 down-regulated) were identified. Moreover, integrated bioinformatics analyses including gene ontology, lncRNA functional prediction based on coding-noncoding gene co-expression network, interactive miRNAs, and transcription factor binding motifs were all carried out to decode the potential functional roles of these newly identified DE-lncRNAs. This work hence offers new resource and insight into lncRNAs for further understanding the molecular mechanisms of tumorigenesis of NKC, and may also define new biomarkers or therapy targets for the translational studies of NKC.


Assuntos
Carcinoma/genética , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Biomarcadores , Carcinogênese/genética , Regulação para Baixo , Humanos , MicroRNAs/isolamento & purificação , Carcinoma Nasofaríngeo , RNA Longo não Codificante/isolamento & purificação , RNA Mensageiro/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
17.
Sci Rep ; 6: 24246, 2016 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-27048930

RESUMO

High-pressure Raman spectroscopy and x-ray diffraction of Sb2S3 up to 53 GPa reveals two phase transitions at 5 GPa and 15 GPa. The first transition is evidenced by noticeable compressibility changes in distinct Raman-active modes, in the lattice parameter axial ratios, the unit cell volume, as well as in specific interatomic bond lengths and bond angles. By taking into account relevant results from the literature, we assign these effects to a second-order isostructural transition arising from an electronic topological transition in Sb2S3 near 5 GPa. Close comparison between Sb2S3 and Sb2Se3 up to 10 GPa reveals a slightly diverse structural behavior for these two compounds after the isostructural transition pressure. This structural diversity appears to account for the different pressure-induced electronic behavior of Sb2S3 and Sb2Se3 up to 10 GPa, i.e. the absence of an insulator-metal transition in Sb2S3 up to that pressure. Finally, the second high-pressure modification appearing above 15 GPa appears to trigger a structural disorder at ~20 GPa; full decompression from 53 GPa leads to the recovery of an amorphous state.

18.
PLoS One ; 11(4): e0153939, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27100390

RESUMO

Blockade of IL-10 signalling clears chronic viral and bacterial infections. Immunization together with blockade of IL-10 signalling or relatively low level of IL-10 further enhances viral and bacterial clearance. IL-10 functions through binding to interleukin 10 receptor (IL-10R). Here we showed that peptides P1 and P2 with the hydrophobic and hydrophilic pattern of the IL10R-binding helix in IL-10 could bind with either IL-10R1 or IL-10, and inhibit inflammatory signals with long duration and negligible cytotoxicity in vitro. Furthermore, P2 can enhance antigen specific CD8+ T cell responses in mice induced by the vaccine based on a long peptide of protein E7 in a human papillomavirus type 16.


Assuntos
Interleucina-10/antagonistas & inibidores , Proteínas E7 de Papillomavirus/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/farmacologia , Sequência de Aminoácidos , Animais , Feminino , Papillomavirus Humano 16/imunologia , Humanos , Imunização , Interleucina-10/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Conformação Proteica , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ressonância de Plasmônio de Superfície , Vacinas de Subunidades Antigênicas/imunologia
19.
Artigo em Chinês | MEDLINE | ID: mdl-27033571

RESUMO

OBJECTIVE: To evaluate the effect of cervical esophagostomy for the treatment of patients with dysphagia induced by radiotherapy, in order to improve the therapeutic effects. METHODS: A retrospective study was performed on 53 nasopharyngeal carcinoma (NPC) patients with dysphagia, who received cervical esophagostomy. The nutritional status of these patients was measured at five given time before and after operation. The occurrence of pneumonia and reflux esophagitis before and after operation was recorded, and the quality of life based on SF-36 quality of life (QOL) scale was studied. RESULTS: After operation, the nutritional status of these patients improved substantially, including the weight, levels of hemoglobin, total protein, albumin and transferring (P<0.05). The pneumonia-infection decreased from 60.38% (32/53) before operation to 15.22% (7/46) after operation (χ(2)=21.04, P<0.01). The incidences of reflux esophagitis decreased from 26.42% (14/53)without operation to 6.52% (3/46) after operation (χ(2)=5.00, P<0.01). Meanwhile, the status of physical health, mental health as well as physical function and social function of these patients were improved significantly at 1 month, 6 months, 1 year and 2 years after operation (P<0.05). CONCLUSION: Cervical esophagostomy can improve the life quality of patients with dysphagia induced by radiotherapy for nasopharyngeal carcinoma.


Assuntos
Transtornos de Deglutição/cirurgia , Esofagostomia , Neoplasias Nasofaríngeas/radioterapia , Qualidade de Vida , Radioterapia/efeitos adversos , Carcinoma , Transtornos de Deglutição/complicações , Esofagite Péptica/complicações , Humanos , Incidência , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicações , Pneumonia/complicações , Estudos Retrospectivos
20.
Hum Vaccin Immunother ; 12(3): 599-606, 2016 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-26367244

RESUMO

Late stage solid tumors cause significant cancer mortality rates worldwide and effective therapy remains a big challenge. Cancer therapeutic vaccines elicit tumor specific T cells that kill tumor cells yet often fail to result in tumor destruction because of the limited T cell response and the local immune-suppressive environment. Blocking interleukin 10 (IL-10) signaling at the time of therapeutic vaccination elicits much stronger T cell responses than vaccination without IL-10 blocking. Anaerobic oncolytic bacteria target hypoxic regions of the late stage tumor tissues which not only stops tumor growth but also provides a pro-inflammatory environment that may increase the effectiveness of a therapeutic vaccine by recruiting more effector T cells to tumor site. In this review, we argue that combining both bacterial and vaccine therapies may improve the efficiency of late stage cancer management.


Assuntos
Bactérias Anaeróbias/patogenicidade , Vacinas Anticâncer/imunologia , Terapia Combinada/métodos , Interleucina-10/antagonistas & inibidores , Neoplasias/terapia , Transdução de Sinais , Animais , Humanos , Resultado do Tratamento
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